Special requirements are made with regard to dosage inhalators intended for local administration of drugs to the respiratory tract and to the lungs. Since mostly very potent drugs are to be administered, the dose accuracy must be great. The dosage of active compound that is to be administered may be as small as 0.1 mg. It is also necessary that the particles that leave the dosage inhalator have a suitable size distribution, since too big particles tend to be deposited in the mouth.
A typical formulation of isoproteranol sulfate powder intended for administration as an aerosol is described in the U.S. Pharmacopeia of July 1, 1980 as being sufficiently powdered that the great majority of individual particles are less than 5 m in diameter. The British Pharmaceutical Codex of 1973 similarly discloses that in both ergotamine sulfate aerosols and isoprenaline sulfate aerosols most the individual particles have a diameter of not more than 5 m.
Several systems are available for local administration of drugs to the respiratory tract and to the lungs. Among these systems may be mentioned nebulizing devices, powder inhalators wich are activated by the air flow generated at inhalation, pressurized aerosols and pump inhalators.
The available systems work but are not without disadvantages.
The nebulizing devices, which are driven by a compressor, by compressed gases or by ultrasound, are relatively big and bulky and are mainly intended for stationary use. They are complicated to use. The drug administration must continue during a fairly long period of time, 5 to 10 minutes.
The use of powder inhalators has been increasing during the last few years. They are activated by the air flow generated at inhalation. When the patient inhales through the inhalator the active compound in solid, micronized form, usually kept in a capsule, is mixed with the inhaled air and administered to the respiratory tract and to the lungs of the patient. These inhalators require, of technical reasons connected with the dispensing of the active compound, a fairly great amount of active compound, 20 mg or more, in order to give an acceptable dosage accuracy. They are, therefore, only useful for low-active compounds, or for high-active compounds in combination with diluting agents, usually lactose. They are cumbersome to load and to clean, and as a rule several inhalations are necessary in order to empty a capsule. Furthermore, they are difficult to handle for certain categories of patients, and the diluting agent, lactose, is irritating at inhalation and may increase the frequency of caries.
The pressurized aerosols are today most widely used at ambulatory treatment. Normally, they comprise a pressure unit that contains the propellant, most often different types of halogenated hydrocarbons, e.g. Freon.RTM., together with the active compound which is either dissolved in the propellant or suspended in the propellant in solid, micronized form. Dosage aerosols where a unit dosage of the active compound is kept separated from the propellant have also been described. Usually surface active compounds and lubricating agents are added in order to obtain a suspension which can be stored and in order to make the dosage mechanism work. The propellants, most widely used, may, furthermore, have undesirable toxicological and environmental effects.
The so called pump inhalators, finally, make use of compressed air as propellant. The active compound is normally in the form of a solution. The compression of the air is obtained by a piston system, but it is difficult in a simple manner to generate a pressure which is sufficiently high to permit an adequate particle size distribution. Furthermore, it is difficult to obtain an exact measuring of dosages of the active compound.